Evaluation of the Feasibility of using Urine IP-10 as a Biomarker to Assess the Treatment Response to the Pharmacotherapy of Active Pulmonary Tuberculosis in the Intensive and Continuation Phase

  • Padmaja Sukumar Postgraduate, Department of Pharmacology, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, Chengalpattu, Tamil Nadu, India.
  • Ruckmani Arunachalam Former Professor and Head, Department of Pharmacology, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, Chengalpattu, Tamil Nadu, India.
  • Meenakshi Narasimhan Professor and Head, Department of Respiratory Medicine, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, Chengalpattu, Tamil Nadu, India.
Keywords: Pulmonary Tuberculosis, Urine IP-10, Biomarker

Abstract

Introduction: Tuberculosis is well known for its chronicity, treatment failures, and drug resistance. Interferon-gamma Inducible Protein 10 (INF IP-10) has been reported to be relatively specific for assessing the severity of tuberculosis, and it can be easily estimated in both urine and blood.
Objective: To determine whether urinary IP-10 levels can be used as a biomarker for monitoring treatment response in patients with active Pulmonary Tuberculosis (PTb).
Materials and Method: 40 participants were enrolled. Urine samples were collected at diagnosis, at the end of 1st, 2nd & 6 months. Sputum smear and culture were done at diagnosis, end of 2nd and 6th month. IP-10 levels were estimated and correlated with treatment response.
Results: All the patients were positive for Mycobacterium Tuberculosis (Mtb) at baseline. At the end of 2nd and 6 months, all of them became smear and culture-negative. The mean urine IP-10 values at diagnosis, end of 1st, 2nd and 6th month were 10.76 ± 2.76, 15.37 ± 3.09, 21.83 ± 4.10 and 8.38 ± 2.46 pg/dl. IP-10 levels increased following intensive therapy and decreased significantly towards the end of treatment. The mean values of IP-10 at baseline, at the end of 2nd and 6th month were correlated with mean scores of clinical symptoms at respective time points. Pearson’s linear correlation was done which showed that IP-10 values and clinical symptoms did not correlate with each other with p=0.836.
Conclusion: Increase in IP-10 level during the intensive therapy indicates the response to treatment and bacterial clearance. Hence urinary IP-10 can be considered as biomarker for monitoring treatment response in PTb patients.

How to cite this article:
Sukumar P, Arunachalam R, Narasimhan M. Evaluation of the Feasibility of using Urine IP-10 as a Biomarker to Assess the Treatment Response to the Pharmacotherapy of Active Pulmonary Tuberculosis in the Intensive and Continuation Phase. J Commun Dis. 2022;54(4):36-40.

DOI: https://doi.org/10.24321/0019.5138.2022100

References

World Health Organization [Internet]. Global tuberculosis report; 2021 [cited 2022 Nov 18]. Available from: https://www.who.int/publications/i/item/9789240037021

Laurenzi M, Ginsberg A, Spigelman M. Challenges associated with current and future TB treatment. Infect Disord Drug Targets. 2007;1;7(2):105-19. [PubMed] [Google Scholar]

Babu S. Biomarkers for treatment monitoring in tuberculosis: a new hope. EBioMedicine. 2017;26:13-4. [PubMed] [Google Scholar]

Petrone L, Cannas A, Vanini V, Cuzzi G, Aloi F, Nsubuga M, Sserunkuma J, Nazziwa RA, Jugheli L, Lukindo T, Girardi E, Antinori A, Pucci L, Reither K, Goletti D. Blood and urine inducible protein 10 as potential markers of disease activity. Int J Tuberc Lung Dis. 2016;1;20(11):1554-61. [PubMed] [Google Scholar]

Vazirinejad R, Ahmadi Z, Arababadi MK, Hassanshahi G, Kennedy D. The biological functions, structure and sources of CXCL10 and its outstanding part in the pathophysiology of multiple sclerosis. Neuroimmunomodulation. 2014;21(6):322-30. [PubMed] [Google Scholar]

Zeissig S, Murata K, Sweet L, Publicover J, Hu Z, Kaser A, Bosse E, Iqbal J, Hussain MM, Balschun K, Röcken C, Arlt A, Günther R, Hampe J, Schreiber S, Baron JL, Moody DB, Liang TJ, Blumberg RS. Hepatitis B virus induced lipid alterations contribute to natural killer T cell-dependent protective immunity. Nat Med. 2012;18:1060-8. [PubMed] [Google Scholar]

Ciesielski CJ, Andreakos E, Foxwell BM, Feldmann M. TNFα-induced macrophage chemokine secretion is more dependent on NF-κB expression than lipopolysaccharides-induced macrophage chemokine secretion. Eur J Immunol. 2002;32:2037-45. [PubMed] [Google Scholar]

Ohmori Y, Hamilton TA. The interferon-stimulated response element and a κB site mediate synergistic induction of murine IP-10 gene transcription by IFN-γ and TNF-α. J Immunol. 1995;154:5235-44. [PubMed] [Google Scholar]

Shields PL, Morland CM, Salmon M, Qin S, Hubscher SG, Adams DH. Chemokine and chemokine receptor interactions provide a mechanism for selective. T cell recruitment to specific liver compartments within hepatitis C-infected liver. J Immunol. 1999;163:6236-43. [PubMed] [Google Scholar]

Dillman JF 3rd, McGary KL, Schlager JJ. An inhibitor of p38 MAP kinase downregulates cytokine release induced by sulfur mustard exposure in human epidermal keratinocytes. Toxicol In Vitro. 2004;18:593-9. [PubMed] [Google Scholar]

Ohmori Y, Hamilton TA. Cell type and stimulus specific regulation of chemokine gene expression. Biochem Biophys Res Commun. 1994;198:590-6. [PubMed] [Google Scholar]

Treacy O, Ryan AE, Heinzl T, O’Flynn L, Cregg M, Wilk M, Odoardi F, Lohan P, O’Brien T, Nosov M, Ritter T. Adenoviral transduction of mesenchymal stem cells in vitro responses and in vivo immune responses after cell transplantation. PLoS One. 2012;7:e42662. [PubMed] [Google Scholar]

Hassanshahi G, Patel SS, Jafarzadeh AA, Dickson AJ. Expression of CXC chemokine IP-10/Mob-1 by primary hepatocytes following heat shock. Saudi Med J. 2007;28:514-8. [PubMed] [Google Scholar]

Ge MQ, Ho AW, Tang Y, Wong KH, Chua BY, Gasser S, Kemeny DM. NK cells regulate CD8+ T cell priming and dendritic cell migration during influenza A infection by IFN-γ and perforin-dependent mechanisms. J Immunol. 2012;189:2099-109. [PubMed] [Google Scholar]

Petrone L, Cannas A, Aloi F, Nsubuga M, Sserumkuma J, Nazziwa RA, Jugheli L, Lukindo T, Girardi E, Reither K, Goletti D. Can blood or urine IP-10 discriminate between active and no active tuberculosis in children? Eur Respir J. 2015;46(suppl 59):PA3635. [Google Scholar]

Lighter J, Rigaud M, Huie M, Peng CH, Pollack H. Chemokine IP-10 an adjunct marker for latent tuberculosis infection in children. Int J Tuberc Lung Dis. 2009;1;13(6):731-6. [PubMed] [Google Scholar]

Yong YK, Tan HY, Saeidi A, Wong WF, Vignesh R, Velu V, Eri R, Larsson M, Shankar EM. Immune biomarkers for diagnosis and treatment monitoring of tuberculosis current developments and future prospects. Front Microbiol. 2019;18;10:2789. [PubMed] [Google Scholar]

Mertaniasih NM, Ananda IG, Soedarsono S, Kusumaningrum D. Diagnosis based on detection of CXCL10 in urine as biomarker for the determining diagnosis of active lung tuberculosis. Indones J Trop Infect Dis. 2021;27;9(1):57-65.

Kim SY, Kim J, Kim DR, Kang YA, Bong S, Lee J, Kim S, Lee NS, Sim B, Cho SN, Kim YS, Lee H. Urine IP-10 as a biomarker of therapeutic response in patients with active pulmonary tuberculosis. BMC Infect Dis. 2018;1;18(1):240. [PubMed] [Google Scholar]

Arun Kumar R, Maignana Kumar R, Duraivel M, Ahamed Basha A, Amalan Stanley V, Ruckmani A. A single centre, prospective, randomized, open labelled clinical study to evaluate the effectiveness of Siddha Poly Herbal Formulation, Viprotm, towards the management of uncomplicated respiratory infection. Biomed Pharmacol J. 2021;30;14(2):793-802. [Google Scholar]

Cannas A, Calvo L, Chiacchio T, Cuzzi G, Vanini V, Lauria FN, Pucci L, Girardi E, Goletti D. IP-10 detection in urine is associated with lung diseases. BMC Infect Dis. 2010;10(1):333. [PubMed] [Google Scholar]

Azzurri A, Sow OY, Amedei A, Bah B, Diallo S, Peri G, Benagiano M, D’Elios MM, Mantovani A, Del Prete G. IFN-γ-inducible protein 10 and pentraxin 3 plasma levels are tools for monitoring inflammation and disease activity in Mycobacterium tuberculosis infection. Microbes Infect. 2005;1;7(1):1-8. [PubMed] [Google Scholar]

Saini H, Mrigpuri P, Menon B, Sonal S. Role of IP-10 during follow up of pulmonary tuberculosis patients. Monaldi Arch Chest Dis. 2022;27;92(4). [PubMed] [Google Scholar]

Published
2022-12-31